Reconstructing transmission trees for communicable diseases using densely sampled genetic data

Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting w...

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Main Authors: Worby, Colin J., O'Neill, Philip D., Kypraios, Theodore, Robotham, Julie V., De Angelis, Daniela, Cartwright, Edward J.P., Peacock, Sharon J., Cooper, Ben S.
Format: Article
Published: Institute of Mathematical Statistics 2016
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Online Access:https://eprints.nottingham.ac.uk/42771/
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author Worby, Colin J.
O'Neill, Philip D.
Kypraios, Theodore
Robotham, Julie V.
De Angelis, Daniela
Cartwright, Edward J.P.
Peacock, Sharon J.
Cooper, Ben S.
author_facet Worby, Colin J.
O'Neill, Philip D.
Kypraios, Theodore
Robotham, Julie V.
De Angelis, Daniela
Cartwright, Edward J.P.
Peacock, Sharon J.
Cooper, Ben S.
author_sort Worby, Colin J.
building Nottingham Research Data Repository
collection Online Access
description Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation.
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spelling nottingham-427712020-05-04T17:40:37Z https://eprints.nottingham.ac.uk/42771/ Reconstructing transmission trees for communicable diseases using densely sampled genetic data Worby, Colin J. O'Neill, Philip D. Kypraios, Theodore Robotham, Julie V. De Angelis, Daniela Cartwright, Edward J.P. Peacock, Sharon J. Cooper, Ben S. Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation. Institute of Mathematical Statistics 2016-03-25 Article PeerReviewed Worby, Colin J., O'Neill, Philip D., Kypraios, Theodore, Robotham, Julie V., De Angelis, Daniela, Cartwright, Edward J.P., Peacock, Sharon J. and Cooper, Ben S. (2016) Reconstructing transmission trees for communicable diseases using densely sampled genetic data. Annals of Applied Statistics, 10 (1). pp. 395-417. ISSN 1941-7330 Bayesian inference Infectious disease Epidemics Outbreak investigation Transmission routes http://projecteuclid.org/euclid.aoas/1458909921#info doi:10.1214/15-AOAS898 doi:10.1214/15-AOAS898
spellingShingle Bayesian inference
Infectious disease
Epidemics
Outbreak investigation
Transmission routes
Worby, Colin J.
O'Neill, Philip D.
Kypraios, Theodore
Robotham, Julie V.
De Angelis, Daniela
Cartwright, Edward J.P.
Peacock, Sharon J.
Cooper, Ben S.
Reconstructing transmission trees for communicable diseases using densely sampled genetic data
title Reconstructing transmission trees for communicable diseases using densely sampled genetic data
title_full Reconstructing transmission trees for communicable diseases using densely sampled genetic data
title_fullStr Reconstructing transmission trees for communicable diseases using densely sampled genetic data
title_full_unstemmed Reconstructing transmission trees for communicable diseases using densely sampled genetic data
title_short Reconstructing transmission trees for communicable diseases using densely sampled genetic data
title_sort reconstructing transmission trees for communicable diseases using densely sampled genetic data
topic Bayesian inference
Infectious disease
Epidemics
Outbreak investigation
Transmission routes
url https://eprints.nottingham.ac.uk/42771/
https://eprints.nottingham.ac.uk/42771/
https://eprints.nottingham.ac.uk/42771/